The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections in immunocompromised hosts, and colonizes the lungs of individuals with cystic fibrosis (Hoiby, N. (1974) Acta Patholgica Microbiol. Scand. Sect. B. 82, 551-558; Reynolds, H. Y., Levine, A. S., Wood, R. E., Zierdt, C. H., Dale, D. C. and Pennington, J. L. (1975) Ann. Intern. Med. 82, 819-832). This bacterium produces a number of extracellular virulence factors including exotoxin A, which is encoded by the toxA gene (Iglewski, B. H. and Kabat, D. (1975) Proc. Natl. Acad. Sci. USA. 72, 22842288; Iglewski, B. H., Sadoff, J. C., Bjorn, M. J., and Maxwell, E. S. (1978) Proc. Natl. Acad. Sci. USA. 75, 3211-3215), two elastolytic proteases, encoded by the lasA and lasB genes, and an alkaline protease encoded by the aprA gene (Morihara, K. and Homma, J. Y. (1985) in Bacterial Enzymes and Virulence, ed. Holder, I. A. (CRC Press, Boca Raton, Fla.) pp. 41-79; Bever, R. A. and Iglewski, B. H. (1988) J. Bacteriol. 170, 4309-4313; Kessler, E. and Saffrin, M. (1988) J. Bacteriol. 170, 5241-5247).
Autoinducer molecules are capable of regulating the gene expression of certain microorganisms. Bycroft et al. (WO92/18614) describe a class of autoinducer molecules which includes N-(β-ketocaproyl) L-homoserine lactone and N-(β-hydroxybutyryl) homoserine lactone. All of the exemplified autoinducer molecules of Bycroft et al. contain C1-C7 side chains. However, autoinducer molecules with side chains of greater length or cyclic side chains are not exemplified by Bycroft et al.
Bycroft et al. state that Pseudomonas aeruginosa is affected by N-(β-ketocaproyl) homoserine lactone. As recently as 1993, researchers have believed that N-(β-ketocaproyl) homoserine lactone is the autoinducer molecule of P. aeruginosa. (Stewart, G. S. A. B. and P. Williams (1993) ASM News, 59, 241-46)